Colorectal cancer is the second leading cause of cancer deaths in the United States. In 1995, there were about 160,000 new cases of colorectal cancers with 60,000 deaths resulting from the disease. One of the requirements for progress in understanding the etiology and improving the treatment of this disease is the development of new animal models in which normal tissue biology and all stages of carcinogenesis can be investigated. The tools are in place to prepare new mouse models for cancer research;what is needed is a continuing dialog between basic and clinical researchers about the molecular biology of human tumors, their initiation and progression with respect to biological correlates and modeling in mice and rats. To this end, the meeting proposed in this application will be hosted by The Jackson Laboratory in Bar Harbor Maine on October 19-22, 2010. Rather than scheduling a series of lectures, we are designing this conference to address six sets of current issues in half-day sessions: 1) Susceptibility/resistance genetic factors and GWAS, 2) Stem and progenitor cells;(poly)clonality;culturing crypts and epithelia, 3) Genomic (in)stability (CIN and MIN) and epigenetic factors (CIMP): The multiple pathway hypothesis;somatic mutations and epimutations;biomarkers for diagnosis and prognosis;serrated, squamous, and rectal tumors;longitudinal studies, 4) Dysplasia;EMT;polarity;(a)symmetric cell division;progression, 5) Inflammation and environmental risk factors;intestinal flora;chemoprevention, and 6) Early detection;therapeutic targets. Each Session will be chaired by an active Rapporteur. We intend to schedule the half-day sessions for morning (9 - 12:30) and afternoon (2:30 - 6:00), each with a 30- minute break. Each session will typically have two 20-minute talks and six 10-minute talks, with five minutes for discussion after each talk. The Rapporteur will provide 10 minutes of introduction at the beginning and lead 10 minutes of general discussion at the end of each half-day session. We believe that the field of research on colon cancer is reaching an exciting point, one that deserves an interactive conference involving both senior and junior investigators. Furthermore, the setting in Bar Harbor will provide a venue in which this sort of conference can thrive, in contrast to larger conferences in urban settings where speakers give lectures and then meet only with pre-determined colleagues. PUBLIC HEALTH RELEVANCE: Colon cancer remains one of the leading health threats in the U.S. today. In order to realize the development of effective models of human cancer, it is critical that basic and clinical researchers maintain clear lines of communication that promote a complete bilateral understanding of the disease and its phenotypes in animal models and how this translates to the study and treatment of the human disease. )